Work

Modulations in HLA-DR expression in visceral leishmaniasis infection

Year: 2016

Type: article

Abstract: Background: HLA class II is a highly polymorphic cell surface glycoprotein, crucial for regulating host immune responses and thereby determining the disease outcome in visceral leishmaniasis by their ability to present the foreign antigens to CD4+ T lymphocytes and activating the T-cells. The complex regulation of HLA class II in different cellular compartments through class II transactivator gene (CIITA) determines the triggering and maintenance of immune responses and has vital role in determining the parasite clearance. The complex transcriptional regulation by CIITA is mediated upon its nuclear import by IFN-γ and hence regulating the expression of HLA-DR. This study tries to provide answer to the complex regulation of HLA-DR mediated via. CIITA at the gene as well as the functional level in visceral leishmaniasis cases. Methods & Materials: The study was performed on whole blood/PBMC and splenic aspirates from VL cases pre-/post-treatment and endemic control groups whole blood/PBMC. Gene(mRNA) expression was performed with the peripheral blood mononuclear cells(PBMC)and the splenic aspirates while the surface(protein) expression was performed with the whole blood and splenic aspirates from cases pre-/post-treatment. Results: There was significantly lower expression of DRB1 (p = 0.047) in active cases compared to healthy controls but there were no significant differences in DRB1 expression in active cases compared to paired cured cases in either PBMC (p = 0.848) or splenic aspirates (p = 0.628) while CIITA expression was higher at post-treatment as compared to pre-treated cases in splenic aspirates as well as the PBMC. At the cellular level, HLA-DR was significantly increased on CD14, CD16 and CD19 positive populations while CD4+ cells were having lowered kinetics of expression upon drug cure in splenic as well as the whole blood. Conclusion: We found that the HLA-DR expression by cell types was similar in splenic aspirates as well as the whole blood assays but there were functional differences in the levels of HLA-DR expression at the gene as well as the protein level. The variable levels of expression of HLA-DR on macrophages and B-cells indicates for targeting these cell populations for modulating the immune responses by altering the antigen processing and presentation abilities hence designing the therapeutic/prophylactic options for VL.

Source: International Journal of Infectious Diseases

DOI: 10.1016/j.ijid.2016.02.442